1. Field of the Invention
Oncogenes are genes that, when activated or altered, may be involved in transformation of normal cells to a neoplastic phenotype. Numerous oncogenes have been identified in both humans and animals, and the transformation mechanisms associated with each vary widely. Frequently, the oncogene has a corresponding normal cellular gene referred to as a proto-oncogene, and modification of either the expression or the structure of the proto-oncogene may result in neoplatic transformation. For example, alteration of a single nucleotide in the ras proto-oncogene renders the host cell neoplastic, while transposition of the c-myc proto-oncogene results in increased expression and neoplastic transformation of the host. Another such example would be translocation of the c-abl proto-oncogene which results in a unique transcript and protein found in chronic myelogenous leukemia (CML).
N-myc is a human proto-oncogene which was originally identified because of its similarity to the viral c-myc oncogene. Gene amplification and/or increased expression of N-myc has been found in certain tumor cell lines as well as both primary and metastatic tumors. In particular, N-myc has been associated with neuroblastomas, retinoblastomas, and small-cell lung cancers (SCLC). Additionally, expression of N-myc has been found to complement mutant ras genes in tumorigenic conversion of rat fibroblasts. Thus, N-myc appears to be involved in the pathogenesis of certain human malignancies.
It would be desirable to isolate and characterize the N-myc gene product and to provide assay methods and reagent compositions useful for identifying and diagnosing tumors in which N-myc is expressed. In particular, it would be desirable to obtain antigenic reagents capable of eliciting antibodies specific for the N-myc gene product and to use such antibodies in diagnosis and treatment of N-myc related cancers.
2. Description of Pertinent References
N-myc proto-oncogenes were first identified in human neuroblastoma cell lines which showed a 25 to 700-fold amplification of the gene. Schwab et al. (1983) Nature 305:245, and Kohl et al. (1983) Cell 35:359. The sequence of the N-myc gene is reported in Kohl et al. (1986) Nature 319:73. Amplification and increased transcription of N-myc in untreated primary neuroblastomas and retinoblastomas are reported in Brodeur et al. (1984) Science 224:1121; Seeger et al. (1985) New Engl. J. Med. 313:1111; and Lee et al. (1984) Nature 309:458. Amplification and increased transcription of N-myc have also been observed in human small-cell lung cancers. Nau et al. (1986) Proc. Natl. Acad. Sci. U.S.A. 83:1092-1096.